MicroRNAs are small, 22 nucleotide-long, non-coding RNAs that regulate gene expression via binding to the 3 UTR of target genes, which results in the suppression of protein translation and decreased mRNA stability. Here, we hypothesized that microRNAs modulate the pathogenesis of asthma. A genome wide screen of the lung microRNA transcriptome was utilized to identify microRNAs whose expression is altered in an experimental murine model of house dust mite-induced asthma. In addition, the effect of corticosteroid treatment on microRNA expression was assessed. Ongoing work is directed at generating mice that conditionally express or delete candidate microRNA genes in lung cells. We have generated a transgenic mouse that over-expresses one of the candidate microRNA genes, which will be utilized to characterize its role in the pathogenesis of asthma. We have also created plasmids to generate conditional knock-out mice for two additional candidate microRNA genes that may modulate the pathogenic manifestations of asthma. We are in the process of generating ES clones for one of these constructs that will be utilized for production of a conditional knock-out mouse.